Five genes derived from human GWAS were tested in our in-vitro assay (ZBTB38, SORCS1, STMN2, RCHY1 and RARB), three of which (ZBTB38, SORCS1 and STMN2) showed a highly significant reduction in susceptibility in knocked-down cell lines, providing the first functional evidence of a role in prion disease. This evidence concerns the gene ZBTB38 and prion disease.